Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities

Abstract

Neonatal sepsis remains a major health issue worldwide, especially for low-birth weight and premature infants, with a high risk of death and devastating sequelae. Apart from antibiotics and supportive care, there is an unmet need for adjunctive treatments to improve the outcomes of neonatal sepsis. Strong and long-standing research on adult patients has shown that vascular endothelium is a key player in the pathophysiology of sepsis and sepsis-associated organ failure, through a direct interaction with pathogens, leukocytes, platelets, and the effect of soluble circulating mediators, in part produced by endothelial cells themselves. Despite abundant evidence that the neonatal immune response to sepsis is distinct from that of adults, comparable knowledge on neonatal vascular endothelium is much more limited. Neonatal endothelial cells express lower amounts of adhesion molecules compared to adult ones, and present a reduced capacity to neutralize reactive oxygen species. Conversely, available evidence on biomarkers of endothelial damage in neonates is not as robust as in adult patients, and endothelium-targeted therapeutic opportunities for neonatal sepsis are almost unexplored. Here, we summarize current knowledge on the structure of neonatal vascular endothelium, its interactions with neonatal immune system and possible endothelium-targeted diagnostic and therapeutic tools for neonatal sepsis. Furthermore, we outline areas of basic and translational research worthy of further study, to shed light on the role of vascular endothelium in the context of neonatal sepsis.

ECMO for Neonatal Sepsis in 2019

“…During sepsis, the difference between neonates, children, and adults have also been described at the level of endothelium and interaction between pathogen and immune system (28). Differently from adults, neonates have reduced recruitment of polymorphonucleate cells (PMN) to the site of infection, diminished phagocytic activity, and intracellular killing by reactive oxygen radicals, and a higher pathogen load per ml of blood as part as a "microbe-tolerant" strategy (29,30).…”

Exploring the Role of Fusobacterium nucleatum in Preterm Birth: A Narrative Review

“…This enables reason to conceptualize the role of periodontal infection process in abstraction from the restriction of limited confined infection as the condition of its ability of sustaining a low-grade systemic inflammatory status [24]. The construction of this theory and expansion of the role of peripheral inflammation has posed essential questions for analysis of the dysregulation of oral microbiome [25], [26]. Therefore, the potential damaging effect of periodontal pathogens in pregnant women is its tendency to cause low-grade systemic inflammation, which may lead to premature rupture of membranes [18].…”

“…Whether the impact from periodontal infection influences or explicates a direct effect is uncertain but suggests a potentially damaging interaction between periodontitis and preterm delivery (PTD) [23]. From the empirical findings, a clear interest focused on the placental inflammation has emerged [1], [4], [25], [26], [27], [28], [29]. Central relationship between the periodontal disease and preterm birth (PTB) is due to an inflammatory response system responding to signal from bacterial invasion [30], [31].…”

“…Specifically, it has been investigated the role of the Gram-negative periodontal pathogen FN, an opportunistic pathogen agent having a specific role in the pathogenesis of different periodontal conditions, and it is increasingly recognized as an important agent of PTB [42], [50]. FN is credited with the distinction of being the most crucial pathogen implicated in the pathogenesis of periodontitis [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], counting its systemic effects on immune system [59], [60]. The localized infection and inflammation of the mouse placenta mediated by oral FN colonization have been described previously by several researchers who suggested that the hematogenous transmission of this bacterium had a detrimental effect on pregnancy, producing intrauterine inflammatory response [51].…”

Identification of Key mRNAs and lncRNAs in Neonatal Sepsis by Gene Expression Profiling

“…Adult sepsis has been studied in depth, but many abundant studies stated that the neonatal immune response to sepsis is different from adults; comparable research on neonatal vascular endothelium is not enough. Neonatal endothelial cells expressing lower amounts of adhesion molecules show a reduced capacity to reactive oxygen species [3]. In the past decades, emerging studies showed activation of lymphocytes, neutrophils, and mononuclear macrophages played crucial roles in the progression of neonatal sepsis.…”